Researchers discover key information about the structure of cholesterol in cell membranes

A new study by Rice University researchers led by Jason Hafner may open new avenues for understanding how cholesterol influences cell membranes and their receptors, paving the way for future research into diseases related to membrane organization. The research was published in the Journal of Physical Chemistry.

Cholesterol is one of the key molecules in biomembranes, complex structures composed of proteins and lipids. It plays a crucial role in the organization of the membrane and influences the behavior of the receptors embedded in it. But understanding the structure and interactions of cholesterol in biomembranes has long been an obstacle for researchers.

“Our breakthrough could have important implications for understanding diseases related to cell membrane function, particularly cancer, where membrane organization is critical,” said Hafner, professor of physics, astronomy and chemistry.

To address this challenge, Hafner’s lab turned to Raman spectroscopy, a technique that uses laser light to scatter molecules and produce detailed vibrational spectra, providing rich molecular information.

The researchers examined cholesterol molecules embedded in membranes and compared their observed spectra with those calculated using density functional theory, a method commonly used in quantum mechanical calculations.

“This process allowed us to observe the unique vibrations of each molecule and learn more about their structure,” Hafner said.

The research team calculated the Raman spectra of 60 different cholesterol structures, focusing on cholesterol’s unique fused ring structure and its eight-carbon chain. Through this process, the researchers discovered that these structures could be grouped based on how the chain deviated from the plane of the rings, a finding that sheds light on previously unknown structural variations.

This study marks the first time that researchers have directly measured cholesterol chain structures in their natural membrane environment, Hafner said.

“We were surprised to find that all cholesterol molecules in the same group had identical spectra at low frequencies,” Hafner said. “This allowed us to simplify the analysis and adapt our experimental data to map the structures of membrane cholesterol chains.”

Other authors of the study include Rice physics graduate student Kyra Birkenfeld, Rice bioengineering undergraduate student Tia Gandhi, and Mathieu Simeral, a former Rice graduate student and current postdoctoral associate at Weill Cornell Medicine.